ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury， as well as the protective role of Huoxue Huayu Jiedu prescription （HXHYJDF） against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups： sham group， model group， deferoxamine （DFO） group （100 mg·kg^-1）， low-dose HXHYJDF group （4.52 g·kg^-1）， medium-dose HXHYJDF group （9.04 g·kg^-1）， and high-dose HXHYJDF group （18.07 g·kg^-1）， with ten rats in each group. Except for the sham group， the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1^st， 3^rd， 5^th， and 7^th days post-reperfusion using the modified neurological severity scores （m-NSS）. Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin （HE） staining and transmission electron microscopy. The contents of malondialdehyde （MDA）， glutathione （GSH）， divalent iron ions （Fe²⁺）， and reactive oxygen species （ROS） in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot （WB） were used to detect the expression of iron death marker proteins glutathione peroxidase 4 （GPX4）， ferroportin-1 （FPN1）， transferrin receptor protein 1 （TfR1）， and ferritin mitochondrial （FtMt） in brain tissue. ResultsCompared with the sham group， the mNSS score of the model group was significantly increased （P<0.01）. HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced， and the intercellular space was widened. The nucleus was fragmented， and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded， and the mitochondrial cristae decreased. The matrix was lost and vacuolated， and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS increased significantly （P<0.01）. The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased （P<0.01）， and the expression of FtMt and TfR1 proteins was significantly increased （P<0.01）. Compared with those of the model group， the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3^rd and 5^th days， respectively （P<0.05， P<0.01）. The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS decreased significantly （P<0.05， P<0.01）. The content of GSH in the low-dose HXHYJDF group increased significantly （P<0.01）， and the contents of MDA and ROS decreased significantly （P<0.01）. The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly （P<0.01）， and the expression of FtMt and TfR1 decreased significantly （P<0.01）. The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly （P<0.05）， and the expression of TfR1 decreased significantly （P<0.01）. WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose， medium-dose， and low-dose HXHYJDF groups were significantly up-regulated （P<0.01）， and the expression levels of FtMt and TfR1 proteins were significantly down-regulated （P<0.01）. ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury， improve the pathological morphology of the infarcted brain tissue， and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury， with increased levels of MDA， Fe²⁺， ROS， and TfR1 and decreased levels of FtMt， FPN1， GPX4， and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins， promoting the discharge of free iron， reducing brain iron deposition， alleviating oxidative stress， and inhibiting ferroptosis.

Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

Pathology is the gold standard for diagnosis of neoplastic diseases.Whole slide imaging turns traditional slides into digital images,and artificial intelligence has shown great potential in pathological image analysis,especially deep learning models.The application of artificial intelligence in whole slide imaging of lung cancer involves many aspects such as histopathological classification,tumor microenvironment analysis,efficacy and survival prediction,etc.,which is expected to assist clinical decision-making of accurate treatment.Limitations in this field include the lack of precisely annotated data and slide quality varying among institutions.Here we summarized recent research in lung cancer pathology image analysis leveraging artificial intelligence and proposed several future directions.

Objective:To clarify the changes of intrahepatic ultrasound hemodynamics before and after hepatic artery thrombosis (HAT) after liver transplantation (LT), providing early warning and anticoagulation guidance to clinicians.Methods:The clinical data of patients who underwent liver transplantation at Zhongshan Hospital of Fudan University between June 2006 and October 2022 were retrospectively analyzed, 47 patients with a diagnosis of HAT confirmed by DSA (digital subtraction angiography) were included in the HAT group, and 71 patients without vascular complications were included in the non-HAT group. Differences in peak flow velocity (PSV), resistance index (RI), and portal vein velocity (PVV) were compared between the two groups. Logistic regression analysis was used to determine the relationship between postoperative PSV decline and HAT occurrence, while ROC curve were used to determine the critical value and evaluate the diagnostic efficacy. Patients with HAT were divided into well-treatment group and poor-treatment group according to whether the blood flow was restored after multiple surgeries or thrombolytic treatments. The changes of early intrahepatic hemodynamics after surgical or thrombolytic therapy were compared between the two groups.Results:①A decrease in PSV of the transplanted hepatic artery was measured 1 d before HAT, and PSV<0.39 m/s predicted thrombus formation with a sensitivity of 0.70, specificity of 0.86, and the AUC was 0.83. ②After treatment, PSV in the HAT group increased immediately, approaching the normal level on the 2nd day. In the well-treatment group, PSV and PVV reached normal levels on the first day after treatment, which were significantly higher than the corresponding values in the poor-treatment group ( P=0.030, 0.021). Conclusions:In the early stage after liver transplantation, a PSV<0.39 m/s is related to the occurrence of HAT thrombosis 1 d later. A significant increase in PSV on the first day after treatment indicates a good treatment response, and there is no need for further DSA re-examination or increasing the number of thrombolysis.

With the development of chest CT screening, surgically resected lung tumors have shifted from predominantly large masses to predominantly small nodules. The intraoperative frozen diagnosis of pulmonary small nodules faces many challenges, such as the accurate understanding about the concepts of adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic adenocarcinoma, as well as their differential diagnosis with small size invasive adenocarcinoma, benign tumors (such as bronchiolar adenoma, sclerosing pneumocytoma, etc.), metastatic tumors and so on. This study summarizes some common problems encountered in the intraoperative frozen diagnosis of small pulmonary nodules in daily practice, focusing on the diagnosis and differential diagnosis of adenocarcinoma, in order to make the accurate intraoperative frozen diagnosis of small pulmonary nodules and diminish misdiagnosis.

Objective:To investigate the clinicopathological features and differential diagnosis of primary pulmonary hyalinizing clear cell carcinoma (HCCC), as well as its diagnostic pitfalls in assessing biopsy specimens.Methods:Five cases of primary pulmonary HCCC diagnosed in the Department of Pathology, Shanghai Chest Hospital, Shanghai, China from August 2019 to December 2023 were collected. The clinicopathological characteristics, immunohistochemistry, and the EWSR1 gene related translocation and fusion were summarized, and relevant literature was reviewed.Results:Among the five cases of HCCC, two were males and three were females, with ages ranging 36-74 years. The tumors were located in the lumen of the bronchus or trachea and showed an exophytic polypoid growth pattern. The maximum diameter of the tumors ranged from 1.3 to 5.0 cm. Histologically, the tumor cells showed transparent cytoplasm and slight cellular atypia, with medium-sized round cells arranged in cords, nests, and trabecula. Small nucleoli were noted, while mitotic figures were rare. The interstitial bands of the tumor in various thickness were anastomosed with hyalining and sclerosing fibrous tissues. All the tumor cells were positive for CKpan, CK7, p40, p63 and CK5/6, but negative for S-100, SMA, Calponin, TTF1 and Napsin A; Ki-67 proliferation index was less than 10% (1%-10%). FISH testing showed EWSR1 gene translocation in all cases, three of which were confirmed by next generation sequencing to have EWSR1::ATF1 gene fusion.Conclusions:Biopsy specimens of primary HCCC in the lungs are prone to misdiagnosis due to the expression of squamous cell carcinoma biomarkers, which poses a unique challenge. A complete understanding of the morphological characteristics of primary pulmonary HCCC, combined with immunohistochemistry and molecular testing, is helpful to reach accurate diagnosis.

Neuroimaging is increasingly widely used in the field of ADHD research,and more and more studies have shown that ADHD patients have structural abnormalities such as reduced cortical volume,thinning thickness,and reduced surface area,which are related to complex clinical symptoms and abnormal brain function in patients.However,the use of neuroimaging to identify biomarkers as an objective diagnostic tool for ADHD still faces many challenges.Multimodal studies can be used to explore the relationship between the structure and function of different brain regions in ADHD patients,and to use neuroimaging to reveal the mechanism of the evolution of clinical symptoms in the whole life cycle of ADHD patients.

Objective This study aimed to analyze the impact of genetic factors on the clinical presentation of tic disorder and investigate the pathogenesis of tic disorder considering different sources of genetic influence and generations,along with the distribution characteristics of evidence from Chinese medicine.Methods Inclusion of 474 cases of tic disorder was assembled(from October,2020 to October,2023),and clinical data on the children,including gender,age of onset,disease duration,initial symptoms,severity,comorbidities,and family history,and TCM patterns were collected.Firstly,the children were divided into genetic and nongenetic groups based on family history,and their clinical manifestations were observed.Secondly,the age of peak incidence of tic disorder in China(6 or 9 years)was used as the age segmentation point to explore the influence of heredity on clinical manifestations at different ages and the distribution of TCM patterns.Finally,children with genetically-related tic disorder were selected as probands to carry out family studies.The morbidity of the first-degree,second-degree and third-degree relatives of the probands were investigated to analyze the morbidity characteristics and distribution of TCM patterns of children with tic disorder under different genetic types.Results Out of 474 children,226 cases(47.7％)belonged to the genetic group,and 248 cases(52.3％)to the nongenetic group.Compared with the non-genetic group,the genetic group had a younger age of onset(P=0.013),a longer duration of illness(P=0.011),a higher degree of severity(P＜0.01),and more comorbid conditions(P=0.016).Children in the genetic group with an age of onset under 6 years accounted for a larger proportion of the liver-hyperactive and wind-driven pattern(26.5％)and a smaller proportion of the qi depression transforming into fire pattern(17.1％),which were significantly different from those in the non-genetic group(P=0.016).In the genetic group,146 cases(64.6％)were inherited from the father,80 cases(35.4％)from the mother,and there was no significant difference in the developmental characteristics of children with tic disorder from different sources of genetic influence.Furthermore,183 cases(81.0％)were inherited from the parent-child generation,26 cases(11.5％)from the second generation,and 17 cases(7.5％)from the third generation;the difference in initial symptoms between different genetic generations was statistically significant(P=0.042).Conclusion Children with genetically related tic disorder have a younger age of onset,their condition is more severe,and they are more likely to be comorbid with other psychiatric disorders.The variation in the distribution of Chinese medicine patterns among children with tic disorder of different ages of onset.

Objective:To discuss the postoperative survival of the gastric cancer patients with different expression levels of myeloid ecotropic viral integration site 1(MEIS1),and to analyze the predictive value of MEIS1 expression in the prognosis evaluation of gastric cancer.Methods:In a gastric cancer survival cohort,215 patients who underwent radical gastrectomy were selected.Immunohistochemical staining was used to detect the expression levels of MEIS1 in both gastric cancer and adjacent normal tissues.The relationship between expression level of MEIS1 and the clinicopathological characteristics of the patients were analyzed by x2 test or Fisher's exact probability method;survival curves were plotted by Kaplan-Meier method;the differences in survival of the patients between MEIS1 high expression group and MEIS1 low expression group were compared by Log-rank test;multivariate Cox proportional hazards regression model was used to calculate the hazard ratios(HR)and 95％confidence intervals(CI)to assess the relationship between MEIS1 expression level and the survival of the gastric cancer patients.Results:The immunohistochemical staining result showed that the expression level of MEIS1 in gastric cancer tissue was decreased.The univariate analysis results showed that the patients with high MEIS1 expression had a longer overall survival than those with low expression(P=0.049),and had a better prognosis.The multivariate Cox proprotional hazards regression analysis results showed that the low MEIS1 expression and high TNM stage were the independent risk factors for poor prognosis of the patients with gastric cancer(HR=1.577,95％CI:1.011-2.460,P=0.045;HR=2.709,95％CI:1.708-4.297,P＜0.001).Conclusion:The gastric cancer patients with low expression of ME1S1 have a shorter postoperative overall survival;MEIS1 is a promising biomarker for prognosis assessment of the patients after radical gastrectomy.

Tooth ankylosis is a clinical condition where the tooth cementum directly fuses with the surrounding alveolar bone,leading to functional and aesthetic defects.The etiology involves genetic,metabolic,and local stimulation factors.The diagnosis of tooth ankylosis requires a combination of clinical manifestations and imaging examinations to improve the diagnostic accuracy.The treatment of tooth ankylosis presents significant challenges.Orthodontic treatment combined with other disciplines offers a new,comprehensive treatment approach,integrating traditional orthodontic techniques with osteotomy,distraction osteogenesis,orthodontic bone traction,corticotomy,dislocation,and autologous tooth transplantation techniques.The treatment of tooth ankylosis requires the cooperation of multiple disciplines,and the experts from orthodontics,oral surgery,and oral medicine collaborate to develop the optimal treatment plan.This comprehensive treatment method achieves better outcomes compared with traditional treatments.This review discusses the etiology,diagnosis,and orthodontic combined multidisciplinary treatment methods of tooth ankylosis,analyzes the advantages and disadvantages of various treatment options,evaluates the efficacy and risks,and provides new perspectives for the treatment of tooth ankylosis.